Sargassum serratifolium C. Agardh (Phaeophyceae, Fucales) is a marine brown alga that belongs to the family Sargassaceae. It is widely distributed throughout coastal areas of Korea and Japan. S. serratifolium has been found to contain high concentrations of plastoquinones, which have strong anti-
cancer, anti-inflammatory,
antioxidant, and neuroprotective activity. This study aims to investigate the anti-diabetic activity of S. serratifolium and its major constituents through inhibition of
protein tyrosine phosphatase 1B (PTP1B), α-
glucosidase, and ONOO--mediated
albumin nitration. S. serratifolium ethanolic extract and fractions exhibited broad PTP1B and α-
glucosidase inhibitory activity (IC50, 1.83~7.04 and 3.16~24.16 µg/mL for PTP1B and α-
glucosidase, respectively). In an attempt to identify bioactive compounds, three plastoquinones (
sargahydroquinoic acid,
sargachromenol and
sargaquinoic acid) were isolated from the active
n-hexane fraction of S. serratifolium. All three plastoquinones exhibited dose-dependent inhibitory activity against PTP1B in the IC50 range of 5.14-14.15 µM, while
sargachromenol and
sargaquinoic acid showed dose-dependent inhibitory activity against α-
glucosidase (IC50 42.41 ± 3.09 and 96.17 ± 3.48 µM, respectively). In the kinetic study of PTP1B
enzyme inhibition,
sargahydroquinoic acid and
sargaquinoic acid led to mixed-type inhibition, whereas
sargachromenol displayed noncompetitive-type inhibition. Moreover, plastoquinones dose-dependently inhibited ONOO--mediated
albumin nitration. Docking simulations of these plastoquinones demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B and α-
glucosidase, indicating that these plastoquinones have high affinity and tight binding capacity towards the active site of the
enzymes. These results demonstrate that S. serratifolium and its major plastoquinones may have the potential as functional food ingredients for the prevention and treatment of
type 2 diabetes.